CGP-12177-racemic-CGP-12177-生命科学试剂-MCE

Hotline:400-820-3792Inhibitors • ScreeningLibraries • Proteinswww.MedChemECGP12177Cat.No.:HY-101393CASNo.:81047-99-6Synonyms:(±)-CGP12177分子式:C₁₄H₂₁N₃O₃分子量:279.33作用靶点:AdrenergicReceptor作用通路:GPCR/GProtein;NeuronalSignaling储存方式:PleasestoretheproductundertherecommendedconditionsintheCertificateofAnalysis.BIOLOGICALACTIVITY生物活性CGP12177((±)-CGP12177)是一种β-肾上腺素能受体(β-AR)配体。CGP12177是β3-AR激动剂(Ki=88nM)，同时具有β1/β2-AR拮抗作用(β1的Ki=0.9nM；β2的Ki=4nM)。CGP12177在大鼠肺动脉中对α1-AR表现出部分激动剂特性。CGP12177可调节NMRI小鼠脂肪组织中ucp和瘦素基因的表达。CGP12177可用于心血管及代谢疾病相关研究[1][2][3][4]。IC50&TargetBeta-1adrenergicBeta-2adrenergicBeta-3adrenergicα1-adrenergicreceptorreceptorreceptorreceptor0.9nM(Ki)4nM(Ki)88nM(Ki)体外研究CGP12177(0.01-100μM)enhancestensioninducedby3μMProstaglandinF2α(PGF2α)(HY-12956)inratintralobarpulmonaryarteriesinaconcentration-dependentmanner,whileinducingconcentration-dependentrelaxationwhenarteriesprecontractedwith30nMPhenylephrine(PHE)(HY-B0769)[1].CGP12177(0.01-100μM)exertsonlyminoreffectonratintralobarpulmonaryarteriesunderbasaltone,butelicitscontractileeffectsandmarkedlypotentiatesPHE-inducedcontractioninthepresenceofPGF2α(3μM)[1].CGP12177(1-100μM)inducesanincreaseinintracellularcalciumconcentrationinratpressurizedarteriesloadedwithFurapentakisester-3(PE-3)andprecontractedwithPGF2α[1].CGP12177(100μM,15min)exhibitsnosignificanteffectonthebasaltoneinratintralobarpulmonaryarteries,butshiftstheconcentration-responsecurvetoPHEtotherightwithoutanychangesinthemaximalresponse[1].CGP12177(1–100μM)-inducedcontractionsinPGF2α-precontractedarteriesaresuppressedby1/3 MasterofBioactiveMolecules—您身边的抑制剂大师www.MedChemEPhentolamine(1μM),Phenoxybenzamine(1μM),SR59230A(3μM),andBupranolol(5μM)inratintralobarpulmonaryarteries[1].CGP12177fullyandconcentration-dependentlydisplaces[3H]prazosin-specificbinding,withapKivalueof5.22[1].CGP12177(0-10μM,30min)doesnotstimulatetheinternalizationofGFP-taggedhumanβ2-adrenoceptorsinCHO-K1cells[2].CGP12177actsasahigh-affinitypartialagonistforcyclicAMPaccumulationandcAMPresponseelement(CRE)-mediatedgenetranscriptioninCHO-K1cellsexpressingthehumanβ2-adrenoceptor[2].体内研究CGP12177(0.05,0.2,0.5and1mg/kg,s.c.,dailyfor15days)stimulatestheexpressionofcertainucpgenesandtheleptingeneconcomitantlyinNMRImiceadiposetissues[3].AnimalModel:MaleNMRImice(4-weeksold)[3]Dosage:0.05,0.2,0.5and1mg/kgAdministration:s.c.,dailyfor15daysResult:SignificantlydecreasedexpressionofthemRNAsforUCP1,UCP2andUCP3inbrownadiposetissue(BAT)atthelowerdosescomparedtocontrol.SlightlyincreasedexpressionofthemRNAsforUCP1,UCP2andUCP3inbrownadiposetissue(BAT)atthehigherdosescomparedtocontrol.MarkedlyenhancedUCP1mRNAexpressioninbothwhiteadiposetissue(WAT)depots(inguinalIWATandepididymalEWAT)inadose-dependentmanner,theincreasewasfromlow(andvariable)basallevelsinIWATandfromundetectablelevelsinEWATofcontrolanimals.UpregulatedUCP3mRNAexpressioninWATespeciallyinEWATand,toalesserextent,inIWAT.DidnotupregulatedUCP2mRNAexpressioninanyWATdepot.ShowedadecreasedexpressionofUCP2mRNAatdoseslowerthan1mg/kginbothIWATandEWAT.RegulatedleptinmRNAlevelsinatissue-dependentmanner.ShowednoeffectonleptinmRNAlevelsinEWATatanydose.Showeda3-foldincreaseofleptinmRNAlevelsinBATat0.5and1mg/kg.Resultedinamaximumof2-foldstimulationinIWATat0.5mg/kg.Didnothaveanyapparenteffectonfoodintake,bodyweightortheweightoftheanalysedfatdepotsatanydosetested.REFERENCESLeblaisV,etal.Roleofalpha-adrenergicreceptorsintheeffectofthebeta-adrenergicreceptorligands,CGP12177,bupranolol,andSR59230A,onthecontractionofratintrapulmonaryartery.JPharmacolExpTher.2004Apr;309(1):137-45.BakerJG,etal.PharmacologicalcharacterizationofCGP12177atthehumanbeta(2)-adrenoceptor.BrJPharmacol.2002Oct;137(3):400-8.2/3 MasterofBioactiveMolecules—您身边的抑制剂大师www.MedChemEOliverP,etal.InvivoeffectsofCGP-12177ontheexpressionofleptinanduncouplingproteingenesinmousebrownandwhiteadiposetissues.IntJObesRelatMetabDisord.2000Apr;24(4):423-8.StrosbergAD,etal.Functionandregulationofthebeta3-adrenoceptor.TrendsPharmacolSci.1996